Investigations
1st investigations to order
incisional biopsy
Test
An incisional biopsy is invariably indicated for most leukoplakias and should be sufficiently large and representative. An excisional biopsy should be avoided.
Benign histological features include ortho/parakeratosis with no sign of keratin in areas deep to the surface (dyskeratosis, a feature of dysplasia). Additionally, a thickening or increase in the overall volume of the spinous or prickle cell layer (acanthosis) is commonly observed. Notably, in the majority of leukoplakias (>60%) only hyperkeratosis with or without acanthosis is found on microscopical analysis.[88]
Microscopical epithelial changes associated with pre-malignancy or epithelial dysplasia include the presence of nuclear pleomorphism and loss of basal polarity.[5] Other features include: increased number of mitotic figures; altered nuclear-cytoplasmic ratio; dyskeratosis or keratin present deep to the superficial layers; altered cellular maturation sequence from basal through surface layers; and fewer or poorer quality of intercellular adhesions or attachment structures.
Result
variable; dysplasia on histological examination; false negatives possible
Investigations to consider
brush biopsy
Test
An oral brush biopsy may be used to exclude dysplasia among common, harmless-appearing oral lesions that do not appear suggestive enough to warrant a scalpel biopsy. Specimen collection is simple, causes little or no pain or bleeding, and requires no anaesthetic; however, accurate sampling of the abnormality is necessary.
The pathology report will recommend a conventional incisional biopsy if significant abnormalities are detected.
Result
variable; may suggest cellular abnormalities; false negatives possible
autoantibodies for anti-nuclear antibody (ANA), double-stranded DNA, and Smith antigen
Test
Performed in anyone suspected of having systemic lupus erythematosus (SLE).
ANA is the best diagnostic test and is positive in virtually all patients with SLE.
Result
normal; elevated if alternative diagnosis
Treponema pallidum serology
Test
Treponemal-specific serology tests are antigen-based tests and remain positive lifelong if current or past infection: tests include treponemal enzyme immunoassay, T pallidum particle agglutination, T pallidum haemagglutination, fluorescent antibody absorption tests, and immunocapture assay.
Non-treponemal titres Venereal Disease Research Laboratory or rapid plasma reagin correlate with disease activity, decreasing or becoming non-reactive with effective treatment.
Result
normal; positive if alternative diagnosis (syphilis)
Emerging tests
chemiluminescent spectroscopy
Test
Testing for autofluorescence or chemiluminescence. The American Dental Association expert panel does not recommend autofluorescence as a triage tool for use in primary care.[93]
Result
may highlight dysplastic areas to guide biopsy site selection
molecular and chromosomal markers
Test
Molecular/gene array studies of tissue may help predict future behaviour and potential for transformation. For example, in assessment of leukoplakia involving so-called high-risk sites, there were greater levels of genetic alterations associated with an elevated risk of progression to carcinoma, by way of high losses of heterozygosity on chromosome 3p and/or 9p sites.[120] DNA ploidy status remains an attractive option in evaluating oral leukoplakia where there has been demonstrated aneuploidy in associated increased risk of progression to squamous carcinoma.[23] Podoplanin, a transmembrane glycoprotein, could be a valuable biomarker in the future for risk assessment of malignant transformation in patients with oral leukoplakia.[121]
Result
variable; may show specific genetic alterations
photodynamic diagnosis (PDD) using 5-aminolevulinic acid (ALA-PDD)
Test
Enables the visualisation of leukoplakia lesions as red fluorescence and has been shown to be successful in detecting oral disorders.[119] Compared with other optical systems, an improvement in the sensitivity and specificity to detect higher grades of dysplasia is described. However, more research is needed before recommending this for routine practice.
Result
compared with low-risk dysplasia and benign lesions, oral cancer and high-risk dysplasia areas have a significantly higher red value and red-to-green ratio
vital staining with toluidine blue
Test
Toluidine blue (TB) is a metachromatic stain that is easily available, economical, and has a high affinity for DNA and RNA. It rapidly stains abnormal tissues, but not normal mucosa. Several studies have demonstrated the ability of TB to detect oral pre-malignant lesions, including oral leukoplakia and oral cancers, with a high sensitivity. However, the stain is also taken up by other ulcerative conditions and, therefore, the specificity of the technique is low.[105] The American Dental Association expert panel does not recommend vital staining as a triage tool for use in primary care.[93]
Result
positive: blue stain
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